alpha-Actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells

Voltage-gated K+ (Kv) channels are particularly important in the physiology of excitable cells in the heart and the brain. PSD-95 is known to cluster Shaker channels and NMDA receptors and the latter is known to couple throug h alpha-actinin-2 to the post-synaptic cytoskeleton [Wyszynski et al, (1997 ) Nature 385, 439-442], but the mechanisms by which Ky channels are linked to the actin cytoskeleton and clustered at specific sites in the heart are unknown. Here we provide evidence that Kv1.5 channels, widely expressed in the cardiovascular system, bind with alpha-actinin-2, Human Kv1.5 interacts via its N-terminus/core region and can be immunoprecipitated with alpha-ac tinin-2 both after in vitro translation and from HEK cells expressing both proteins, The ion channels and alpha-actinin-2 colocalize at the membrane i n HEK cells, where disruption of the actin cytoskeleton and antisense const ructs to alpha-actinin-2 modulate the ion and gating current density. (C) 2 000 Federation of European Biochemical Societies.